Onkológia 2/2012

Molecular-genetic analysis of hereditary breast/ovarian cancer: Results of mutation testing of BRCA1 and BRCA2 genes

Germline mutations in the BRCA1 and BRCA2 genes account for the majority of hereditary breast ovarian cancer (HBOC) cases. Identification of the BRCA pathogenic mutations has a causal clinical impact. However, still after BRCA1 and BRCA2 screening the most HBOC cases remain negative for any mutational event. Accordingly, in these cases raises the relevance to analyse the presence of large genomic rearrangements, unusual variants of uncertain clinical significance and finally possible presence of mutations in moderate risk HBOC genes. We analysed the BRCA1/2 genes in 590 Slovak HBOC families from year 2002 and revealed the presence of pathogenic mutations in 105 families, what represents 17.8%. In the set of 117 and 104 HBOC families, 27 different BRCA1 and 17 BRCA2 variants with uncertain clinical effect were detected. To approve their closer clinical significance we predicted their effect using several prediction softwares. We observed that the best clinical criterion for BRCA1 analysis is presence of breast cancer below 40 years in family history and with the association of presence of ovarian cancer at 50 years.

Keywords: hereditary breast ovarian cancer, BRCA1, BRCA2, genetic analysis, mutation.